Cep63 and Cep152 Cooperate to Ensure Centriole Duplication

Centrosomes consist of two centrioles embedded in pericentriolar material and function as the main microtubule organising centres in dividing animal cells. They ensure proper formation and orientation of the mitotic spindle and are therefore essential for the maintenance of genome stability. Centrosome function is crucial during embryonic development, highlighted by the discovery of mutations in genes encoding centrosome or spindle pole proteins that cause autosomal recessive primary microcephaly, including Cep63 and Cep152. In this study we show that Cep63 functions to ensure that centriole duplication occurs reliably in dividing mammalian cells. We show that the interaction between Cep63 and Cep152 can occur independently of centrosome localisation and that the two proteins are dependent on one another for centrosomal localisation. Further, both mouse and human Cep63 and Cep152 cooperate to ensure efficient centriole duplication by promoting the accumulation of essential centriole duplication factors upstream of SAS-6 recruitment and procentriole formation. These observations describe the requirement for Cep63 in maintaining centriole number in dividing mammalian cells and further establish the order of events in centriole formation.中心体（centrosome）由嵌入于中心粒外周物质（pericentriolar material）的两个中心粒（centriole）组成，是分裂期动物细胞内主要的微管组织中心（microtubule organising centre）。它们保障有丝分裂纺锤体（mitotic spindle）的正确形成与定向，因此对维持基因组稳定性（genome stability）至关重要。中心体功能在胚胎发育（embryonic development）过程中不可或缺：编码中心体或纺锤体极蛋白的基因突变可引发常染色体隐性遗传性原发性小头畸形（autosomal recessive primary microcephaly），Cep63与Cep152便是这类致病蛋白的代表。本研究证实，Cep63的功能是保障分裂期哺乳动物细胞内中心粒复制（centriole duplication）的可靠进行。研究表明，Cep63与Cep152之间的相互作用可不依赖于中心体定位（centrosomal localisation）而发生，且二者的中心体定位存在相互依赖性。进一步研究发现，小鼠与人类的Cep63和Cep152可协同作用，通过在SAS-6招募与前中心粒形成（procentriole formation）之前促进关键中心粒复制因子的积累，从而保障高效的中心粒复制。上述结果明确了Cep63在维持分裂期哺乳动物细胞中心粒数目中的必要性，并进一步确立了中心粒形成过程中的事件先后顺序。